The impact of two different rituximab-based strategies in cryoglobulinaemic vasculitis secondary to Sjögren's disease: a monocentric cohort study.

OBJECTIVES: To compare two different rituximab (RTX)-based therapeutic approaches on vasculitic and lymphoproliferative-related disease activity and on non-Hodgkin lymphoma (NHL) development in a cohort of patients affected by cryoglobulinaemic vasculitis secondary to Sjögren's disease (Sjögren-CryoVasc). METHODS: Three Sjögren-CryoVasc treatment groups were identified: 1) early RTX induction followed by maintenance; 2) late RTX induction with possible on-demand retreatment; 3) no RTX treatment. The following outcomes were evaluated: a) changes in cumulative ESSDAI, considering vasculitic-related and lymphoproliferative-related domains and changes in ESSDAI specific to each single vasculitic-related and lymphoproliferative-related domain; b) development of NHL; c) occurrence of persistent hypogammaglobulinemia associated with serious infections. RESULTS: 13 Sjögren-CryoVasc patients were identified: 1) 5/13 treated earlier with RTX with subsequent maintenance; 2) 5/13 treated late with RTX with possible on-demand retreatment; 3) 3/13 not treated with RTX. The two RTX groups showed a decrease in the ESSDAI score with group 1 showing the most substantial reduction (p=0.028). Patients receiving RTX exhibited significant improvement in cutaneous, PNS, and articular vasculitic-related ESSDAI domains (p=0.007; p=0.006; p=0.03, respectively). By contrast RTX did not greatly affect the lymphoproliferative-related ESSDAI domains, even if an improvement was noted in the glandular and nodal domains for group 1 (p=0.03; p=0.03, respectively). No differences in NHL occurrence or safety concerns were observed among the groups. CONCLUSIONS: RTX is an effective and safe treatment to control Sjögren-CryoVasc disease activity with a greater impact when administered earlier with a maintenance regimen. RTX alone cannot, however, affect the possible evolution of Sjögren-CryoVasc into an overt NHL.

Systemic vasculitis: one year in review 2024.

Systemic vasculitides comprise a collection of rare and heterogeneous disorders capable of impacting any organ and system, posing a considerable burden of mortality and comorbidity. As with previous annual reviews of this series, this review will offer a critical overview of the latest literature on pathogenesis, biomarkers, and treatment options in both small- and large-vessel vasculitis.

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity.

PURPOSE: Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series. METHODS: The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies. RESULTS: A significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%, p < 0.005), and the use of immunomodulators was associated to a higher risk to get infected (p = 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without (p < 0.01). Patients' older age (≥ 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 (p = 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination (p = 0.0039) and also after the booster dose (p = 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity (p = 0.029). CONCLUSIONS: The present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Physical activity assessment with wearable devices in rheumatic diseases: a systematic review and meta-analysis.

OBJECTIVES: In the management of rheumatic musculoskeletal disorders (RMDs), regular physical activity (PA) is an important recognized non-pharmacological intervention. This systematic review and meta-analysis aims to evaluate how the use of wearable devices (WDs) impacts physical activity in patients with noninflammatory and inflammatory rheumatic diseases. METHODS: A comprehensive search of articles was performed in PubMed, Embase, CINAHL and Scopus. A random-effect meta-analysis was carried out on the number of steps and moderate-vigorous physical activity (MVPA). Univariable meta-regression models were computed to assess the possibility that the study characteristics may act as modifiers on the final meta-analysis estimate. RESULTS: In the analysis, 51 articles were included, with a total of 7488 participants. Twenty-two studies considered MVPA outcome alone, 16 studies considered the number of steps alone, and 13 studies reported information on both outcomes. The recommended PA threshold was reached for MVPA (36.35, 95% CI 29.39, 43.31) but not for daily steps (-1092.60, -1640.42 to -544.77). Studies on patients with fibromyalgia report a higher number (6290, 5198.65-7381.62) of daily steps compared with other RMDs. Patients affected by chronic inflammatory arthropathies seemed to fare better in terms of daily steps than the other categories. Patients of younger age reported a higher overall level of PA than elderly individuals for both the number of steps and MVPA. CONCLUSION: Physical activity can be lower than the recommended threshold in patients with RMDs when objectively measured using WD. WDs could be a useful and affordable instrument for daily monitoring physical activity in RMDs and may support an increase in activity levels. PROSPERO TRIAL REGISTRATION: CRD42021227681, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227681.

Systemic vasculitis: one year in review 2023.

Systemic vasculitides are heterogeneous disabling diseases characterised by chronic inflammation of the blood vessels potentially leading to tissue destruction and organ failure. The recent COVID-19 pandemic has had a significant impact on the epidemiology and management of patients with systemic vasculitis. In parallel, new insights have been provided on systemic vasculitis pathogenetic mechanisms, possible new therapeutic targets, and newer glucocorticoid-sparing treatments with better safety profiles. As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis focusing on precision medicine in vasculitis.

Systemic vasculitis: one year in review 2022.

Systemic vasculitis are rare heterogeneous disorders potentially involving any organ and system with a relevant burden of mortality and comorbidity.As in the previous annual reviews of this series, in this review we will provide a critical digest of the most recent literature regarding pathophysiology, clinical manifestations, diagnostic tools and treatment options in small- and large-vessel vasculitis.

One year in review 2021: systemic vasculitis.

Large- and small-vessel vasculitis are complex potentially life-threatening systemic autoimmune diseases that have recently been subjected to considerable immunologic and clinical research. Following the other reviews of this series, here we aim to summarise some of the most significant studies that have been recently published on the pathogenesis, clinical features and novel treatments of systemic vasculitis.

One year in review 2020: vasculitis.

Systemic vasculitides are a group of diseases that could potentially affect any organ with heterogeneous clinical manifestations that usually depend on the size of the most involved vessels. These diseases could be associated with a relevant burden of mortality and morbidity if not early recognised and treated. Moreover, even if they are usually rare diseases, their incidence and prevalence seem to be increasing in the last decade, partially because of improved awareness and management of vasculitis from physicians. Like in the previous annual reviews of this series, in this paper we revised the most recent literature on pathogenesis, clinical manifestations and treatment options in small- and large-vessel vasculitis.

Data linkage analysis of giant cell arteritis in Italy: Healthcare burden and cost of illness in the Italian region of Friuli Venezia Giulia (2001-2017).

Giant cell arteritis (GCA) is the most common vasculitis in adults. However, comprehensive analyses of the healthcare burden are still scarce. The aim of the study is to report the healthcare burden and cost of illness of GCA in the Friuli Venezia Giulia (FVG) region of Italy, based on a data linkage analysis. To this end, a retrospective study was conducted through the integration of many administrative health databases of the FVG region as the source of information. Cases were identified from two verified, partially overlapping sources (the rare disease registry and medical exemption database). From 2001 to 2017, 208 patients with GCA were registered. The prevalence of GCA in the population aged ⩾ 45 years as of December 31, 2017 was 27.2/100,000 inhabitants (95% CI 23.5-31.4). The mean time of observation was 4.5 ± 3.6 years. A total of 3182 visits (338 per 100 patient-years) was recorded. The most frequent specialty visits were rheumatology (n = 610, 19.2%), followed by internal medicine (n = 564, 17.7%). A total of 287 hospitalizations (30 per 100 patient-years) were reported. A total of 13,043 prescriptions (1386 per 100 patient-years) were registered. More than half of the patients were prescribed an immunosuppressive agent. The overall estimated direct healthcare cost was €2,234,070, corresponding to €2374 per patient-year. Overall, GCA is a rare disease which implies a high healthcare cost.

Faster steroid-free remission with tocilizumab compared to methotrexate in giant cell arteritis: a real-life experience in two reference centres.

Glucocorticoids (GCs) are still the mainstay of treatment of giant cell arteritis (GCA). Although GCs are highly effective in GCA, the high burden of toxicity of GCs as well as the disease relapse during GC tapering is well documented. To compare the efficacy and rapidity of TCZ and MTX as steroid-sparing agents in a real-life cohort of GCA patients. A retrospective analysis was conducted including patients with newly diagnosed GCA from the Rheumatology Units of Udine and Rome. The inclusion criterion was the treatment with TCZ or MTX as first steroid-sparing drug. 112 GCA patients (81 females) with a median age of 70 (IQ 65-75) years were collected. Thirty-one out of 112 (27.7%) patients were treated with TCZ (162 mg/week), while 81/112 (72.3%) patients received MTX (up to 20 mg/week) as a GC-sparing agent. At month 6 after GCA onset, 5/31 (16.1%) patients in TCZ group and none in MTX group were in GC-free sustained remission (p value = 0.001). Similarly, at month 12, 64.5% (20/31) and 11.1% (9/81) of patients were in sustained GC-free remission in TCZ and MTX group, respectively (p value <0.001). At month 24 of follow-up, at least one relapse of the disease occurred in 7/31 (22.6%) in TCZ-treated and 28/81 (34.6%) in MTX-treated patients, respectively (p value = 0.22). TCZ allowed a faster discontinuation of steroid therapy than MTX in GCA patients, without increasing the risk of relapse.

Validation of the Italian version of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire.

Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P < 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P < 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P < 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion: The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL.

Recent updates in the diagnosis and management of cryoglobulinemic vasculitis.

INTRODUCTION: Cryoglobulinemic vasculitis (CV), also known as mixed cryoglobulinemic syndrome (MCS), is a systemic vasculitis that affects small blood vessels. It exhibits a wide range of clinical manifestations, making its treatment a continuing challenge for physicians. AREAS COVERED: We conducted a comprehensive review to evaluate the current status of diagnosis, management, and treatment of mixed cryoglobulinemia (MC). The accurate clinical and serological evaluation plays a vital role in diagnosing MC, identifying potential comorbidities, and monitoring its main manifestations and complications. Treatment strategies should be individualized based on the underlying etiopathogenesis, the severity of organ involvement, and the associated underlying disease. At present, the two mainstays of CV treatment are direct antiviral agents (for HCV-related CV) and B-cell-targeted therapy. EXPERT OPINION: MC remains one of the few autoimmune diseases where the etiology is known, at least for the majority of patients. Its pathogenetic mechanism offers a unique opportunity to investigate the interplay between infections and the immune system. Moving forward, the primary challenge will continue to lie in the treatment of resistant or refractory cases of CV, particularly those associated with autoimmune diseases, or cases classified as 'essential' CV.

Unmet needs in ANCA-associated vasculitis: Physicians' and patients' perspectives.

In recent years, clinical research has increased significantly and therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis have improved. However, there are still unanswered questions and unmet needs about AAV patients. The purpose of this review is to examine the frontiers of research related to emerging biomarkers eventually predicting relapse, and new therapeutic approaches, not to mention new quality of life assessment tools. Identifying predictors of relapse may help optimize therapeutic strategies, minimize disease recurrence, and reduce treatment-related side effects. In addition, it is important to recognize that patients may suffer long-term consequences of the disease and its treatment, which, although life-saving, is often associated with significant side effects. Our goal, therefore, is to highlight what has been achieved, the pitfalls, and what still needs to be done, comparing the views of physicians and patients.

Interstitial lung disease with and without progressive fibrosing phenotype in patients with idiopathic inflammatory myopathies: data from a large multicentric cohort.

OBJECTIVES: Patients with connective tissue diseases can develop interstitial lung disease (ILD), leading to a progressive fibrosing ILD (PF-ILD) phenotype in some cases. We aimed to investigate the occurrence of PF-ILD in idiopathic inflammatory myopathies (IIMs), and factors potentially predicting this phenotype. Secondary aims were to assess the radiological pattern and factors associated with IIMs-ILD. METHODS: Patients with IIMs from our multicentric prospective cohort were retrospectively evaluated. Data were recorded at IIMs and ILD diagnosis, and during follow-up. Patients with ILD were classified according to the predominant high-resolution CT (HRCT) pattern: non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP) and organising pneumonia (OP). PF-ILD was defined according to the 2022 American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS) and Latin American Thoracic Society (ALAT) guidelines. Univariate and multivariate analyses were performed to identify factors associated to ILD and to PF-ILD. RESULTS: Of 253 patients with IIMs, 125 (49%) had ILD: 99 (78%) at IIMs diagnosis and 26 (22%) during follow-up (21/26 within 5 years). Multivariate analysis identified anti-Jo-1, anti-MDA5, anti-Ro52, high score on manual muscle test, mechanic's hands and Raynaud's phenomenon as independently associated with ILD. The predominant HRCT pattern was NSIP (50% of patients), followed by UIP (28%) and OP (22%). At 1-year follow-up, PF-ILD occurred in 18% of IIMs-ILD. PF-ILD was predicted by anti-MDA5, heliotropic rash, xerostomia and xerophthalmia at univariate but not at multivariate analysis. CONCLUSION: Patients with IIM should be carefully screened for ILD at IIMs diagnosis and yearly during follow-up. All patients with IIMs-ILD should be carefully monitored to capture ILD progression since a consistent proportion of them are expected to develop PF-ILD.

Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC).

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.

Safety of Biologic-DMARDs in Rheumatic Musculoskeletal Disorders: A Population-Based Study over the First Two Waves of COVID-19 Outbreak.

This study aims to explore disease patterns of coronavirus disease (COVID-19) in patients with rheumatic musculoskeletal disorders (RMD) treated with immunosuppressive drugs in comparison with the general population. The observational study considered a cohort of RMD patients treated with biologic drugs or small molecules from September 2019 to November 2020 in the province of Udine, Italy. Data include the assessment of both pandemic waves until the start of the vaccination, between February 2020 and April 2020 (first), and between September 2020 and November 2020 (second). COVID-19 prevalence in 1051 patients was 3.5% without significant differences compared to the general population, and the course of infection was generally benign with 2.6% mortality. A small percentage of COVID-19 positive subjects were treated with low doses of steroids (8%). The most used treatments were represented by anti-TNF agents (65%) and anti-IL17/23 agents (16%). More than two-thirds of patients reported fever, while gastro-intestinal symptoms were recorded in 27% of patients and this clinical involvement was associated with longer swab positivity. The prevalence of COVID-19 in RMD patients has been confirmed as low in both waves. The benign course of COVID-19 in our patients may be linked to the very low number of chronic corticosteroids used and the possible protective effect of anti-TNF agents, which were the main class of biologics herein employed. Gastro-intestinal symptoms might be a predictor of viral persistence in immunosuppressed patients. This finding could be useful to identify earlier COVID-19 carriers with uncommon symptoms, eventually eligible for antiviral drugs.